Department of Nephrology and Renal Transplantation, Hôpital Jean Bernard, 2, rue de la Milétrie, CHU Poitiers, 86021 Poitiers, France.
Clin J Am Soc Nephrol. 2011 Sep;6(9):2165-74. doi: 10.2215/CJN.06180710. Epub 2011 Jul 22.
Glomerular deposition of monoclonal Ig has been exceptionally described as the cause of membranoproliferative glomerulonephritis, through activation of the complement alternative pathway (CAP).
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We retrospectively studied six adults with monoclonal gammopathy and glomerulonephritis (GN) characterized by isolated C3 deposits.
All patients presented with hematuria, associated with chronic renal failure and proteinuria in five patients, three of whom had nephrotic syndrome. Five patients had monoclonal gammopathy of undetermined significance and one had smoldering myeloma. The serum monoclonal IgG (κ four of six, λ two of six) was associated with light chain (LC) proteinuria in five patients. Four patients had low serum C3 and/or factor B levels. C4, factor H (CFH), and I protein levels were normal in five of five patients; none had detectable C3NeF. IgG anti-CFH activity was positive in one case. No mutations in CFH, CFI, and MCP genes were identified in four of four patients. Deposits were intramembranous, subepithelial, and mesangial by electron microscopy, and stained positive for C3 (six of six), properdin, and CFH (two of two) but negative for Ig LC and heavy chains, C4, and C1q (6/6) by immunofluorescence. Five patients progressed to end-stage renal disease over a median period of 47 months, despite chemotherapy in four patients. In one patient, monoclonal λLC deposits were observed on a follow-up kidney biopsy after 4 years.
GN with isolated glomerular C3 deposits might represent an unusual complication of plasma cell dyscrasia, related to complement activation through an autoantibody activity of the monoclonal Ig against a CAP regulator protein.
通过补体替代途径（CAP）的激活，单克隆免疫球蛋白在肾小球中的沉积已被特别描述为膜增生性肾小球肾炎的病因。
设计、环境、参与者和测量方法：我们回顾性研究了 6 例伴有单克隆丙种球蛋白血症和肾小球肾炎（GN）的成年人，其特征为孤立的 C3 沉积。
所有患者均出现血尿，5 例伴有慢性肾衰竭和蛋白尿，其中 3 例出现肾病综合征。5 例患者存在意义未明的单克隆丙种球蛋白血症，1 例存在冒烟型骨髓瘤。6 例患者中有 4 例血清单克隆 IgG（κ 型 4 例，λ 型 2 例）与轻链（LC）蛋白尿相关。4 例患者血清 C3 和/或因子 B 水平较低。5 例患者的 C4、因子 H（CFH）和 I 蛋白水平正常；均未检测到 C3NeF。1 例患者 IgG 抗 CFH 活性阳性。4 例患者中有 4 例未发现 CFH、CFI 和 MCP 基因突变。电镜下沉积物呈内皮下、上皮下和系膜性，免疫荧光染色均为 C3（6/6）、备解素和 CFH（2/2）阳性，而 LC 和重链、C4 和 C1q（6/6）阴性。中位随访 47 个月后，5 例患者进展至终末期肾病，其中 4 例接受化疗。1 例患者在 4 年后的肾活检中观察到单克隆 λ LC 沉积。
伴有孤立性肾小球 C3 沉积的 GN 可能代表浆细胞异常的一种不常见并发症，与单克隆 Ig 通过针对 CAP 调节蛋白的自身抗体活性引起的补体激活有关。
